Macrophage reprogramming—rather than depletion—is efficacious in a specific subset of colorectal tumor models Article Swipe
Noha-Ehssan Mohamed
,
Raheleh Amirkhah
,
Xabier-Cortes Lavaud
,
Kathryn Gilroy
,
Robin Bartolini
,
Eoghan J. Mulholland
,
Abhishek D. Garg
,
Kathryn A.F. Pennel
,
René Jackstadt
,
Rachel A. Ridgway
,
Colin Nixon
,
Phimmada Hatthakarnku
,
Andrew D. Campbell
,
Simon J. Leedham
,
Joanne Edwards
,
Philip D. Dunne
,
Simon T. Barry
,
Gerard J. Graham
,
Owen J. Sansom
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3212822/v1
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.21203/rs.3.rs-3212822/v1
Despite the abundance of macrophages in colorectal cancer (CRC), macrophage-targeted therapy has not demonstrated significant clinical benefit. Here, we show that macrophage populations differ across the consensus molecular subtypes (CMS) of CRC and report the first preclinical study of macrophage targeting using mouse models stratified by CMS class. Whereas pan-macrophage ablation, using a CSF1R-inhibitor, lacked efficacy across CMS classes, genetic deletion of inflammatory chemokine receptors (iCCRs) reprogrammed macrophages towards an anti-tumorigenic phenotype, curtailing tumorigenesis in models of CMS1 CRC. We identify an iCCR-independent anti-tumorigenic antigen-presenting macrophage population necessary for therapeutic efficacy. We further show that individual targeting of the CCR1, CCR2, and CCR5 receptors on CRC macrophages lacks benefit, whereas their combined targeting holds promise. We propose that selective targeting of immunosuppressive macrophage populations, whilst sparing antigen-presenting subsets, should be considered when trialling macrophage-targeted therapies.
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Metadata
- Type
- preprint
- Language
- en
- Landing Page
- https://doi.org/10.21203/rs.3.rs-3212822/v1
- https://www.researchsquare.com/article/rs-3212822/latest.pdf
- OA Status
- green
- References
- 61
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4385554851
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4385554851Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.21203/rs.3.rs-3212822/v1Digital Object Identifier
- Title
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Macrophage reprogramming—rather than depletion—is efficacious in a specific subset of colorectal tumor modelsWork title
- Type
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preprintOpenAlex work type
- Language
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enPrimary language
- Publication year
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2023Year of publication
- Publication date
-
2023-08-03Full publication date if available
- Authors
-
Noha-Ehssan Mohamed, Raheleh Amirkhah, Xabier-Cortes Lavaud, Kathryn Gilroy, Robin Bartolini, Eoghan J. Mulholland, Abhishek D. Garg, Kathryn A.F. Pennel, René Jackstadt, Rachel A. Ridgway, Colin Nixon, Phimmada Hatthakarnku, Andrew D. Campbell, Simon J. Leedham, Joanne Edwards, Philip D. Dunne, Simon T. Barry, Gerard J. Graham, Owen J. SansomList of authors in order
- Landing page
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https://doi.org/10.21203/rs.3.rs-3212822/v1Publisher landing page
- PDF URL
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https://www.researchsquare.com/article/rs-3212822/latest.pdfDirect link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
greenOpen access status per OpenAlex
- OA URL
-
https://www.researchsquare.com/article/rs-3212822/latest.pdfDirect OA link when available
- Concepts
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Reprogramming, Macrophage, Cancer research, Colorectal cancer, Biology, Genetics, Cancer, Cell, In vitroTop concepts (fields/topics) attached by OpenAlex
- Cited by
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0Total citation count in OpenAlex
- References (count)
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61Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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